Acute pancreatitis can range from a mild, self-limiting ­process that responds to supportive care to severe disease with multiple organ failure and high mortality. Its incidence is ­increasing,¹ and pancreatitis is one of the most common causes of hospital admission for gastrointestinal illness.² Although most patients experience minor episodes characterized by mild parenchymal edema without organ dysfunction, response to conservative management, and ­complete recovery,³ approximately 20% to 25% of patients develop clinically severe acute pancreatitis. More severe episodes may progress to pancreatic necrosis, systemic inflammatory response ­syndrome (SIRS), multiorgan failure, clinical deterioration, and even death.⁴ Historically, mortality has been up to 15% in the setting of necrotizing pancreatitis and as high as 30% with infected pancreatic necrosis.⁵ Recent years have seen advances in the classification and management of acute pancreatitis including evidence-based guidelines and a notable shift toward nonoperative management of even the most severe cases of infected pancreatic necrosis.

Given the wide spectrum of severity, patients with pancreatitis must receive highly individualized care. Mild acute pancreatitis can generally be managed with resuscitation and supportive care including a search for etiologic factors such as gallstones. Patients with severe pancreatitis and pancreatic necrosis may require maximal support in intensive care and occasionally surgical or endoscopic debridement of the pancreas. The indications for intervention in patients with severe pancreatitis have evolved significantly in the past 2 decades. Whereas early surgical debridement was used for most patients with pancreatic necrosis in the past, a far more conservative approach was adopted with recognition that surgical debridement was not necessary in the setting of most cases of pancreatic necrosis without infection.⁶ Revision of the 1992 Atlanta Classification of acute pancreatitis⁷ to provide a newer classification to more precisely describe the clinical behavior and imaging characteristics of acute pancreatitis⁸ has allowed more uniform categorization of the disease in recent years. At the same time, the development of minimally invasive and nonsurgical approaches to necrotizing pancreatitis has led to increased consensus that most patients, including even those with the greatest disease severity, may avoid surgical debridement.⁹ This chapter reviews contemporary management strategies in acute pancreatitis, including assessment of severity, nutritional support, the role of antibiotics, and indications for intervention.

Acute pancreatitis has been attributed to a range of etiologic factors (Table 68-1). Intra-acinar activation of trypsinogen, with subsequent activation of other pancreatic enzymes, is thought to play a central role in pathogenesis of the disease. A local inflammatory response is associated with liberation of oxygen-derived free radicals and cytokines including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and platelet-activating factor. These mediators play an essential role in transformation of the local inflammatory response to a systemic illness.

Most cases (70%-80%) of pancreatitis are associated with gallstones or sustained alcohol abuse; the relative frequency of these 2 factors depends on the prevalence of alcohol use in the population studied. Choledocholithiasis is the most common of known mechanical factors.¹⁰ The majority of patients with non–alcohol-related pancreatitis will have gallstones, and many will develop recurrent acute pancreatitis if stones persist. Another known mechanical cause of pancreatitis is instrumentation of the pancreatic or biliary duct; at least 1% of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) develop clinically detectable pancreatitis. Several metabolic processes are associated with pancreatitis, particularly alcohol abuse. Signs and symptoms of pancreatitis can be seen in patients with prolonged alcohol use, usually after 10 years or more of heavy ingestion. Binge drinking has not been related to pancreatitis,¹¹ but its development is thought to be related to consumption of over 4 to 5 drinks per day for more than 5 years.¹² The precise mechanism of this association is not well established.¹³ Several drugs have been related to the development of pancreatitis, particularly corticosteroids, thiazide diuretics, estrogens, azathioprine, and furosemide. ­In approximately 10% of cases, no underlying cause can be identified. Some have suggested that occult biliary microlithiasis may be the etiology in most cases of idiopathic acute pancreatitis.¹⁴ Smoking was thought to be a cofactor in ­alcohol-related pancreatitis, although it is now recognized as an independent risk factor in the disease with risk correlating to the extent of tobacco use.¹⁵

Diagnosis

Early diagnosis and determination of disease severity are essential to guide appropriate therapy. Clinical diagnosis has changed very little in recent years. Clinical signs and symptoms such as upper abdominal pain, back pain, vomiting, fever, tachycardia, and leukocytosis are nonspecific. Although the classically described signs of umbilical and flank bruising may be seen with severe retroperitoneal hemorrhage (Cullen and Grey-Turner signs), these are rare in all but the most severe cases, are nonspecific, and may be seen with any cause of retroperitoneal bleeding. Therefore, diagnosis depends on clinical suspicion and demonstration of elevated plasma levels of pancreatic enzymes. In the setting of characteristic abdominal symptoms and/or characteristic imaging, serum amylase levels of amylase or lipase 3 times the upper limit of normal secure the diagnosis.¹ Levels of both amylase and lipase peak within the first 24 hours of symptoms, and amylase has a slightly shorter plasma half-life. Serum lipase, therefore, has a slightly higher sensitivity for detection, as elevations occur earlier and last longer than serum amylase.¹⁶ Furthermore, hyperamylasemia is not entirely specific for pancreatitis and is seen occasionally with other causes of abdominal pain such as tumors of the ovaries or even kidney failure.¹⁷ Simultaneous determination of serum lipase and amylase only marginally improves the diagnosis of acute pancreatitis. Of note, plasma levels of pancreatic enzymes are useful for diagnosis but not for prognosis or assessment of disease severity, and absolute levels have no correlation with severity.

Assessment of disease severity is important for the initiation of goal-directed therapy. However, reproducible measures of disease severity are lacking.¹⁸ Early evaluation is complicated by a nonspecific clinical presentation, and severe disease may present with a fulminant sepsis-like syndrome or in a relatively innocuous manner. Initial signs and symptoms with severe disease are only different in degree from edematous pancreatitis, and both severe and mild forms share the same etiologies.¹⁹ Attempts to identify differences in the pathogenesis of mild and severe disease have not revealed differences, and available clinical models do not accurately predict which patients will progress to severe disease.²⁰

Assessment of Severity

Clinical scoring systems such as the Ranson²¹ or Glasgow²² scores incorporate multiple clinical variables to predict outcomes, comparing variables at admission and over the subsequent 48 hours. In Ranson’s original report, the presence of 5 or 6 positive signs was associated with a 40% mortality and prolonged intensive care unit course in 50% of patients, whereas the presence of 7 or 8 signs was associated with a nearly 100% mortality. However, these systems require 48 hours from admission for full assessment, and current data suggest they are poor predictors of disease severity.²³ The Acute Physiology and Chronic Health Evaluation II (APACHE II) system is another physiologic scoring system that estimates disease severity based on quantifying multiple variables. Higher APACHE II scores at admission are associated with higher mortality, and data may be calculated within the first 24 hours. Despite this advantage, APACHE II scores in the first 24 hours have been found to have a limited positive predictive value of only 43% for severe acute pancreatitis. Updates that include clinical assessment of obesity (APACHE-O) or additional clinical variables (APACHE III) have been proposed, but all updates have proven to be nonspecific with high false-positive rates, are somewhat unwieldy to use, and are not commonly incorporated into practice.

Numerous individual markers have been investigated as indicators of severity. Brown et al²⁴ and others have shown that hemoconcentration predicts parenchymal necrosis and organ failure. Persistence of hemoconcentration and azotemia despite fluid resuscitation is predictive of severe pancreatitis.²⁵ Increases in C-reactive protein levels with disease severity at 48 hours after admission may help identify severe disease with superior sensitivity and specificity relative to other markers,²⁶ although the delayed peak at 36 to 72 hours after admission leads to decreased efficacy for assessment on admission.

Cross-sectional imaging, particularly contrast-enhanced computed tomography (CT), plays an essential role in evaluation of the progression to severe acute pancreatitis with associated complications. CT findings of simple edematous pancreatitis include enlargement of the pancreas with loss of peripancreatic fat planes, areas of decreased density, and occasional simple fluid collections (Fig. 68-1). The Balthazar scoring system and other similar grading systems incorporate imaging findings such as pancreatic inflammation and peripancreatic collections in an attempt to correlate radiographic appearance with morbidity and mortality.^27,28 CT is particularly useful in its ability to demonstrate pancreatic necrosis. From a baseline of 30 to 50 Hounsfield units (HU), viable pancreas will typically enhance by more than 50 HU with the administration of intravenous (IV) contrast. Nonviable pancreas, however, will not enhance with IV contrast (Fig. 68-2). Various criteria used to diagnose necrosis include nonenhancement of more than 30% of the pancreatic parenchyma or an area greater than 3 cm of the pancreas that does not enhance.⁷ Magnetic resonance imaging (MRI) is sometimes used as an alternative in patients with moderate renal impairment or an allergy to IV contrast. MRI may have comparable sensitivity and specificity to CT for diagnosis of severe acute pancreatitis,²⁹ although MRI is less practical for the critically ill patient.

The timing of and indications for CT in acute pancreatitis require clinical judgment rather than strict criteria. CT scans performed early in the course of the disease will often fail to identify developing local complications, as necrosis may only become evident 2 to 3 days after the onset of symptoms, significantly limiting its utility at admission.³⁰ The sensitivity for identifying pancreatic necrosis using contrast-enhanced CT approaches 100% after 4 days from diagnosis.¹⁸ It is therefore advisable to obtain an abdominal CT with IV contrast in patients with clinical and radiographic features of acute pancreatitis who do not improve after several days of conservative management. Repeat CT may be obtained with signs of clinical deterioration.

CT scan is also essential to facilitate image-guided tissue aspiration in the diagnosis of infected pancreatic necrosis. The development of infected pancreatic necrosis, as discussed below, is an indication for radiographic, endoscopic, or surgical intervention. However, clinical criteria do not easily differentiate severe pancreatitis from infected necrosis. Leukocytosis, fever, and organ failure may be seen with or without infection. Emphysematous pancreatitis, the demonstration of gas within the pancreatic parenchyma, is diagnostic of infection but is uncommonly seen (Fig. 68-3). Image-guided aspiration of the necrotic pancreas can be used to diagnose infected pancreatic necrosis with a high degree of accuracy (Fig. 68-4). CT-guided aspiration is reserved for patients with documented pancreatic necrosis who are not improving clinically or who experience clinical decline.

The sensitivity and specificity for detection of infection with CT-guided aspiration are reported to be 96% and 99%, respectively, with a positive predictive value of 99.5% and a negative predictive value of 95%.³¹ Areas of nonenhancing pancreas are aspirated, with samples sent for aerobic, anaerobic, and fungal culture. In most patients, diagnosis of infection may be made with a positive Gram stain of the aspirate rather than waiting for confirmatory culture.

Infection may occur at any point in the clinical course with pancreatic necrosis, with the incidence of infection increasing up to 3 weeks after presentation. In one study, infection was documented in 49% of patients in the first 14 days, but less than 15% had infection diagnosed after 35 days.³¹ Infection may occur later in the course of the disease, even after a prior negative aspiration. Repeat CT-guided aspiration is therefore often necessary in the setting of clinical decline. In one series of patients with aspiration demonstrating infection, the first aspirate was positive in 17 of 30 patients (57%), although 7 patients (23%) required 2 or more procedures and 6 patients (20%) required 3 or more aspirations to demonstrate infection.³² Fine-needle aspiration should not be performed in the absence of suspected infection due to the small risk of introducing infection into a previously sterile collection.³³

Classification of disease severity is important for the timely administration of appropriate care as well as for the assessment of treatment modalities and standardization of reporting. The Atlanta Classification emerged from an interdisciplinary symposium in 1992.³⁴ This original Atlanta Classification defined acute pancreatitis, organ failure, and local compilations of the disease in an attempt to introduce uniformity in assessment of severity and ­complications. This allowed some descriptive consistency, helping to standardize clinical care and aiding clinical research. Recognition of the deficiencies of this system, particularly the failure to incorporate organ failure, led to the development of the Revised Atlanta Classification (RAC) using a Web-based iterative consultative process.⁸ The RAC defines categories of severity in terms of the following categories: (1) mild acute pancreatitis, with the absence of organ failure and systemic or local complications; (2) ­moderate acute pancreatitis, with transient organ failure and/or local complications requiring prolonged hospital stay or intervention; and (3) severe acute pancreatitis, with persistent organ ­failure. Another severity classification, the ­Determinant-Based Classification (DBC) arose from a meta-analysis of the ­literature.³⁵ The DBC incorporates pancreatic necrosis in the following categories: (1) mild acute pancreatitis, with no pancreatic or peripancreatic necrosis and no organ ­failure; (2) moderate acute pancreatitis, with sterile pancreatic or peripancreatic necrosis and/or transient organ failure; (3) severe acute pancreatitis, with infected pancreatic or peripancreatic necrosis or persistent organ failure; and (4) critical acute pancreatitis, with infected pancreatic or peripancreatic necrosis and persistent organ failure. In addition to assessment of severity, the RAC defines specific morphologic features of acute pancreatitis and its complications (Table 68-2).

Resuscitation and Monitoring

Although patients with acute pancreatitis require management strategies tailored to disease severity, the initial management of patients is increasingly standardized. A cornerstone of this initial management is aggressive fluid resuscitation to replace considerable extravascular or “third space” fluid losses. Volume depletion accounts for the hemoconcentration and azotemia associated with severe pancreatitis.³⁶ Animal data suggest that early aggressive fluid resuscitation prevents pancreatic necrosis,³⁷ and retrospective clinical data suggest that such aggressive fluid resuscitation in the first day after admission reduces complications.^38,39 While aggressive fluid administration does not necessarily prevent the progression to necrosis, patients with inadequate resuscitation have an increased risk of developing pancreatic necrosis.⁴⁰ Fluid resuscitation is particularly important in the initial 24 hours, at rates often exceeding 200 mL/h.²⁵ One randomized controlled trial suggested that the use of lactated Ringer’s solution versus normal saline reduced markers of SIRS.⁴¹ Close monitoring of respiratory, cardiovascular, and renal function is essential to detect and treat hypovolemia. All patients require close assessment of fluid balance, including a Foley catheter. Patients with severe disease should be admitted to an intensive care unit for continuous monitoring.

Nutritional Support

Historically, enteral feeding was limited in the setting of acute pancreatitis for the purpose of providing “pancreatic rest.” Enteral feeding was believed to exacerbate the existing inflammatory process through stimulation of exocrine pancreatic function and release of proteolytic enzymes. Nasogastric tubes were often used for the purpose of avoiding pancreatic stimulation and in the setting of paralytic ileus. No data support the use of nasogastric decompression in the absence of ileus, however. Although brief periods without full oral intake are common on initial presentation, limitation of nutritional intake may have serious consequences in the setting of critical illness with enhanced catabolism and negative nitrogen balance.⁴² In this setting, total parenteral nutrition (TPN) has often been used for nutritional support in an effort to prevent further complications.⁴³